草酸铂治疗进展期结直肠癌疗效与ERCC1、ERCC2/XPD基因多态关联的Meta分析

A Meta-analysis of correlation between oxaliplatin treatment for advanced colorectal cancer and ERCC1, ERCC2/XPD polymorphism

目的评价DNA修复基因ERCC1、ERCC2单核苷酸多态与草酸铂治疗进展期结直肠癌患者疗效之间的相关性。方法在Pub Med、维普数据库以及CNKI数据库全面检索2000-2010年间发表的关于核苷酸切除修复基因多态性与草酸铂治疗结直肠癌疗效关系的队列研究,按纳入标准对文献进行筛选后提取相关信息,应用Revman 4.2软件选择固定效应模型(Peto法)或随机效应模型(D-L法)计算合并RR值及95%可信区间,并进行敏感性分析和发表偏倚的估计。结果本研究纳入国内外8篇合格文献,其中ERCC1 118位点5篇(包括了534例患者),C/C的总反应率为79.19﹪(175/221),C/T和T/T的总反应率为67.73﹪(212/313);异质性检验显示,χ2=5.32,P=0.26,采用固定效应模型分析,合并RR值为1.24,95﹪CI(1.11,1.38)。XPD/ERCC2 751位点3篇(包括了261例患者),C/C的总反应率为57.53﹪(42/73),C/A和A/A的总反应率为64.89﹪(122/188);异质性检验显示,χ2=11.52,P=0.003,采用随机效应模型分析,合并RR值为0.93,95﹪CI(0.43,1.97)。将入选文献的研究对象按人群来源进行亚组分析,结果显示ERCC1 118位点基因多态性与进展期结直肠癌化疗敏感性之间的关系仅见于亚洲人群。漏斗图未发现明显的发表偏倚。结论进展期结直肠癌患者中ERCC1 118位密码子基因型C/C化疗敏感性优于C/T或T/T基因型,尤其在亚洲人群中,这种敏感性尤为突出。而ERCC2 751位密码子C/C基因型化疗敏感性与C/A或A/A基因型之间差异无统计学意义。

【Objective】To evaluate DNA repair gene ERCC1, ERCC2 polymorphism and the efficacy of oxaliplatin treatment for advanced colorectal cancer and their correlation.【Methods】From cohort studies of relationship between nucleotide excision repair gene polymorphisms and the efficiency of oxaliplatin treatment for colorectal cancer published in the Pub Med, VIP database and CNKI database between 2000 and 2010, relevant information was extracted according to the inclusion criteria for screening the literature. The combined RR values and 95% confidence intervals were calculated with fixed effect model（Peto method） or random effects model（D-L method） selected with Revman 4.2 software, and then sensitivity analysis was made and publication bias was estimated.【Results】The study included 8 qualified domestic and foreign literatures, including 5 of ERCC1 loci 118（involving 534 patients）,in which the total reaction rate of C/C was 79.19%（175/221）, total C/T and T/T reaction rate was 67.73%（212/313）.Heterogeneity test showed that χ2=5.32, P =0.26, using a fixed effect model analysis, the combined RR value was1.24, 95% CI was（1.11, 1.38）. There were 3 articles involving XPD/ERCC2 loci 751（including 261 patients）, in which the total reaction rate of C/C was 57.53 %（42/73）, total C/A and A/A reaction rate was 64.89 %（122/188）.Heterogeneity test showed that χ2=11.52, P =0.003, analyzed using random effects model, the combined RR value was 0.93, 95%CI was（0.43, 1.97）. The research objects were included for subgroup analysis according to population;results showed the relationship between ERCC1 118 gene polymorphism and sensitivity of chemotherapy for advanced colorectal cancer existed only in Asian populations. Funnel plot showed no significant publication bias.【Conclusions】In advanced colorectal cancer, the patients with genotype C/C in ERCC1 codon 118 are more sensitive to chemotherapy than those with genotype C/T or T/T, especially in Asian populations. There is no statistically significant difference in chemotherapy sensitivity between the patients with genotype C/C in ERCC2 codon 751 and those with genotype C/A or A/A.